SummaryObesity and diabetes have reached pandemic proportions and new therapeutic strategies are critically needed. Brown adipose tissue (BAT), a major source of heat production, possesses significant energy-dissipating capacity and therefore represents a promising target to use in combating these diseases. Recently, I discovered a novel link between circadian rhythm and thermogenic stress in the control of the conserved, calorie-burning functions of BAT. Circadian and thermogenic signaling to BAT incorporates blood-borne hormonal and nutrient cues with direct neuronal input. Yet how these responses coordinately shape BAT energy-expending potential through the regulation of cell surface receptors, metabolic enzymes, and transcriptional effectors is still not understood. My primary goal is to investigate this previously unappreciated network of crosstalk that allows mammals to effectively orchestrate daily rhythms in BAT metabolism, while maintaining their ability to adapt to abrupt changes in energy demand. My group will address this question using gain and loss-of-function in vitro and in vivo studies, newly-generated mouse models, customized physiological phenotyping, and cutting-edge advances in next generation RNA sequencing and mass spectrometry. Preliminary, small-scale validations of our methodologies have already yielded a number of novel candidates that may drive key facets of BAT metabolism. Additionally, we will extend our circadian and thermogenic studies into humans to evaluate the translational potential. Our results will advance the fundamental understanding of how daily oscillations in bioenergetic networks establish a framework for the anticipation of and adaptation to environmental challenges. Importantly, we expect that these mechanistic insights will reveal pharmacological targets through which we can unlock evolutionary constraints and harness the energy-expending potential of BAT for the prevention and treatment of obesity and diabetes.

Obesity and diabetes have reached pandemic proportions and new therapeutic strategies are critically needed. Brown adipose tissue (BAT), a major source of heat production, possesses significant energy-dissipating capacity and therefore represents a promising target to use in combating these diseases. Recently, I discovered a novel link between circadian rhythm and thermogenic stress in the control of the conserved, calorie-burning functions of BAT. Circadian and thermogenic signaling to BAT incorporates blood-borne hormonal and nutrient cues with direct neuronal input. Yet how these responses coordinately shape BAT energy-expending potential through the regulation of cell surface receptors, metabolic enzymes, and transcriptional effectors is still not understood. My primary goal is to investigate this previously unappreciated network of crosstalk that allows mammals to effectively orchestrate daily rhythms in BAT metabolism, while maintaining their ability to adapt to abrupt changes in energy demand. My group will address this question using gain and loss-of-function in vitro and in vivo studies, newly-generated mouse models, customized physiological phenotyping, and cutting-edge advances in next generation RNA sequencing and mass spectrometry. Preliminary, small-scale validations of our methodologies have already yielded a number of novel candidates that may drive key facets of BAT metabolism. Additionally, we will extend our circadian and thermogenic studies into humans to evaluate the translational potential. Our results will advance the fundamental understanding of how daily oscillations in bioenergetic networks establish a framework for the anticipation of and adaptation to environmental challenges. Importantly, we expect that these mechanistic insights will reveal pharmacological targets through which we can unlock evolutionary constraints and harness the energy-expending potential of BAT for the prevention and treatment of obesity and diabetes.

Max ERC Funding

1 497 008 €

Duration

Start date: 2015-05-01, End date: 2020-04-30

Project acronymBODY-UI

ProjectUsing Embodied Cognition to Create the Next Generations of Body-based User Interfaces

Researcher (PI)Kasper Anders Soren HornbAEk

Host Institution (HI)KOBENHAVNS UNIVERSITET

Call DetailsConsolidator Grant (CoG), PE6, ERC-2014-CoG

SummaryRecent advances in user interfaces (UIs) allow users to interact with computers using only their body, so-called body-based UIs. Instead of moving a mouse or tapping a touch surface, people can use whole-body movements to navigate in games, gesture in mid-air to interact with large displays, or scratch their forearm to control a mobile phone. Body-based UIs are attractive because they free users from having to hold or touch a device and because they allow always-on, eyes-free interaction. Currently, however, research on body-based UIs proceeds in an ad hoc fashion and when body-based UIs are compared to device-based alternatives, they perform poorly. This is likely because little is known about the body as a user interface and because it is unclear whether theory and design principles from human-computer interaction (HCI) can be applied to body-based UIs. While body-based UIs may well be the next interaction paradigm for HCI, results so far are mixed.
This project aims at establishing the scientific foundation for the next generations of body-based UIs. The main novelty in my approach is to use results and methods from research on embodied cognition. Embodied cognition suggest that thinking (including reasoning, memory, and emotion) is shaped by our bodies, and conversely, that our bodies reflect thinking. We use embodied cognition to study how body-based UIs affect users, and to increase our understanding of similarities and differences to device-based input. From those studies we develop new body-based UIs, both for input (e.g., gestures in mid-air) and output (e.g., stimulating users’ muscles to move their fingers), and evaluate users’ experience of interacting through their bodies. We also show how models, evaluation criteria, and design principles in HCI need to be adapted for embodied cognition and body-based UIs. If successful, the project will show how to create body-based UIs that are usable and orders of magnitude better than current UIs.

Recent advances in user interfaces (UIs) allow users to interact with computers using only their body, so-called body-based UIs. Instead of moving a mouse or tapping a touch surface, people can use whole-body movements to navigate in games, gesture in mid-air to interact with large displays, or scratch their forearm to control a mobile phone. Body-based UIs are attractive because they free users from having to hold or touch a device and because they allow always-on, eyes-free interaction. Currently, however, research on body-based UIs proceeds in an ad hoc fashion and when body-based UIs are compared to device-based alternatives, they perform poorly. This is likely because little is known about the body as a user interface and because it is unclear whether theory and design principles from human-computer interaction (HCI) can be applied to body-based UIs. While body-based UIs may well be the next interaction paradigm for HCI, results so far are mixed.
This project aims at establishing the scientific foundation for the next generations of body-based UIs. The main novelty in my approach is to use results and methods from research on embodied cognition. Embodied cognition suggest that thinking (including reasoning, memory, and emotion) is shaped by our bodies, and conversely, that our bodies reflect thinking. We use embodied cognition to study how body-based UIs affect users, and to increase our understanding of similarities and differences to device-based input. From those studies we develop new body-based UIs, both for input (e.g., gestures in mid-air) and output (e.g., stimulating users’ muscles to move their fingers), and evaluate users’ experience of interacting through their bodies. We also show how models, evaluation criteria, and design principles in HCI need to be adapted for embodied cognition and body-based UIs. If successful, the project will show how to create body-based UIs that are usable and orders of magnitude better than current UIs.

Max ERC Funding

1 853 158 €

Duration

Start date: 2015-05-01, End date: 2020-04-30

Project acronymCIRCUITASSEMBLY

ProjectDevelopment of functional organization of the visual circuits in mice

Researcher (PI)Keisuke Yonehara

Host Institution (HI)AARHUS UNIVERSITET

Call DetailsStarting Grant (StG), LS5, ERC-2014-STG

SummaryThe key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.

The key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.

Max ERC Funding

1 500 000 €

Duration

Start date: 2015-04-01, End date: 2020-03-31

Project acronymConTExt

ProjectConnecting the Extreme

Researcher (PI)Sune Toft

Host Institution (HI)KOBENHAVNS UNIVERSITET

Call DetailsConsolidator Grant (CoG), PE9, ERC-2014-CoG

SummaryAdvances in technology and methodology over the last decade, have enabled the study of galaxies to the highest redshifts. This has revolutionized our understanding of the origin and evolution of galaxies. I have played a central role in this revolution, by discovering that at z=2, when the universe was only 3 Gyr old, half of the most massive galaxies were extremely compact and had already completed their star formation. During the last five years I have led a successful group of postdocs and students dedicated to investigating the extreme properties of these galaxies and place them into cosmological context. Combining a series of high profile observational studies published by my group and others, I recently proposed an evolutionary sequence that ties together the most extreme galaxies in the universe, from the most intense dusty starburst at cosmic dawn, through quasars: the brightest sources in the universe, driven by feedback from supermassive black holes, and galaxy cores hosting the densest conglomerations of stellar mass known, to the sleeping giants of the local universe, the giant ellipticals. The proposed research program will explore if such an evolutionary sequence exists, with the ultimate goal of reaching, for the first time, a coherent physical understanding of how the most massive galaxies in the universe formed. While there is a chance the rigorous tests may ultimately reveal the proposed sequence to be too simplistic, a guarantied outcome of the program is a significantly improved understanding of the physical mechanisms that shape galaxies and drive their star formation and quenching

Advances in technology and methodology over the last decade, have enabled the study of galaxies to the highest redshifts. This has revolutionized our understanding of the origin and evolution of galaxies. I have played a central role in this revolution, by discovering that at z=2, when the universe was only 3 Gyr old, half of the most massive galaxies were extremely compact and had already completed their star formation. During the last five years I have led a successful group of postdocs and students dedicated to investigating the extreme properties of these galaxies and place them into cosmological context. Combining a series of high profile observational studies published by my group and others, I recently proposed an evolutionary sequence that ties together the most extreme galaxies in the universe, from the most intense dusty starburst at cosmic dawn, through quasars: the brightest sources in the universe, driven by feedback from supermassive black holes, and galaxy cores hosting the densest conglomerations of stellar mass known, to the sleeping giants of the local universe, the giant ellipticals. The proposed research program will explore if such an evolutionary sequence exists, with the ultimate goal of reaching, for the first time, a coherent physical understanding of how the most massive galaxies in the universe formed. While there is a chance the rigorous tests may ultimately reveal the proposed sequence to be too simplistic, a guarantied outcome of the program is a significantly improved understanding of the physical mechanisms that shape galaxies and drive their star formation and quenching

Max ERC Funding

1 999 526 €

Duration

Start date: 2015-09-01, End date: 2020-08-31

Project acronymCSUMECH

ProjectCholesterol and Sugar Uptake Mechanisms

Researcher (PI)Bjorn Pedersen

Host Institution (HI)AARHUS UNIVERSITET

Call DetailsStarting Grant (StG), LS1, ERC-2014-STG

SummaryCardiovascular disease, diabetes and cancer have a dramatic impact on modern society, and in great part are related to uptake of cholesterol and sugar. We still know surprisingly little about the molecular details of the processes that goes on in this essential part of human basic metabolism. This application addresses cholesterol and sugar transport and aim to elucidate the molecular mechanism of cholesterol and sugar uptake in humans. It moves the frontiers of the field by shifting the focus to in vitro work allowing hitherto untried structural and biochemical experiments to be performed.
Cholesterol uptake from the intestine is mediated by the membrane protein NPC1L1. Despite extensive research, the molecular mechanism of NPC1L1-dependent cholesterol uptake still remains largely unknown.
Facilitated sugar transport in humans is made possible by sugar transporters called GLUTs and SWEETs, and every cell possesses these sugar transport systems. For all these uptake systems structural information is sorely lacking to address important mechanistic questions to help elucidate their molecular mechanism.
I will address this using a complementary set of methods founded in macromolecular crystallography and electron microscopy to determine the 3-dimensional structures of key players in these uptake systems. My unpublished preliminary results have established the feasibility of this approach. This will be followed up by biochemical characterization of the molecular mechanism in vitro and in silico.
This high risk/high reward membrane protein proposal could lead to a breakthrough in how we approach human biochemical pathways that are linked to trans-membrane transport. An improved understanding of cholesterol and sugar homeostasis has tremendous potential for improving general public health, and furthermore this proposal will help to uncover general principles of endocytotic uptake and facilitated diffusion systems at the molecular level.

Cardiovascular disease, diabetes and cancer have a dramatic impact on modern society, and in great part are related to uptake of cholesterol and sugar. We still know surprisingly little about the molecular details of the processes that goes on in this essential part of human basic metabolism. This application addresses cholesterol and sugar transport and aim to elucidate the molecular mechanism of cholesterol and sugar uptake in humans. It moves the frontiers of the field by shifting the focus to in vitro work allowing hitherto untried structural and biochemical experiments to be performed.
Cholesterol uptake from the intestine is mediated by the membrane protein NPC1L1. Despite extensive research, the molecular mechanism of NPC1L1-dependent cholesterol uptake still remains largely unknown.
Facilitated sugar transport in humans is made possible by sugar transporters called GLUTs and SWEETs, and every cell possesses these sugar transport systems. For all these uptake systems structural information is sorely lacking to address important mechanistic questions to help elucidate their molecular mechanism.
I will address this using a complementary set of methods founded in macromolecular crystallography and electron microscopy to determine the 3-dimensional structures of key players in these uptake systems. My unpublished preliminary results have established the feasibility of this approach. This will be followed up by biochemical characterization of the molecular mechanism in vitro and in silico.
This high risk/high reward membrane protein proposal could lead to a breakthrough in how we approach human biochemical pathways that are linked to trans-membrane transport. An improved understanding of cholesterol and sugar homeostasis has tremendous potential for improving general public health, and furthermore this proposal will help to uncover general principles of endocytotic uptake and facilitated diffusion systems at the molecular level.

SummaryG protein-coupled receptors make up both the largest membrane protein and drug target families. DE-ORPHAN aims to determine the close functional context; specifically physiological agonists and signaling pathways; and provide the first research tool compounds, of orphan peptide receptors.
Determination of physiological agonists (aka de-orphanization), by high-throughput screening has largely failed. We will introduce a new research strategy: 1) developing highly innovative bioinformatics methods for handpicking of all orphan receptor targets and candidate ligand screening libraries; and 2) employing a screening technique that can measure all signaling pathways simultaneously.
The first potent and selective pharmacological tool compounds will be identified by chemoinformatic design of focused screening libraries. We will establish the ligands’ structure-activity relationships important for biological activity and further optimization towards drugs.
The first potent and selective Gs- and G12/13 protein inhibitors will be designed by structure-based re-optimization from a recent crystal structure of a Gq-inhibitor complex, and applied to determine orphan receptor signaling pathways and ligand pathway-bias. They will open up for efficient dissection of important signaling networks and development of drugs with fewer side effects.
DE-ORPHANs design hypotheses are based on unique computational methods to analyze protein and ligand similarities and are founded on genomic and protein sequences, structural data and ligands. The interdisciplinary research strategy applies multiple ligands acting independently but in concert to provide complementary receptor characterization. The results will allow the research field to advance into studies of receptor functions and exploitation of druggable targets, ligands and mechanisms. Which physiological insights and therapeutic breakthroughs will we witness when these receptors find their place in human pharmacology and medicine?

G protein-coupled receptors make up both the largest membrane protein and drug target families. DE-ORPHAN aims to determine the close functional context; specifically physiological agonists and signaling pathways; and provide the first research tool compounds, of orphan peptide receptors.
Determination of physiological agonists (aka de-orphanization), by high-throughput screening has largely failed. We will introduce a new research strategy: 1) developing highly innovative bioinformatics methods for handpicking of all orphan receptor targets and candidate ligand screening libraries; and 2) employing a screening technique that can measure all signaling pathways simultaneously.
The first potent and selective pharmacological tool compounds will be identified by chemoinformatic design of focused screening libraries. We will establish the ligands’ structure-activity relationships important for biological activity and further optimization towards drugs.
The first potent and selective Gs- and G12/13 protein inhibitors will be designed by structure-based re-optimization from a recent crystal structure of a Gq-inhibitor complex, and applied to determine orphan receptor signaling pathways and ligand pathway-bias. They will open up for efficient dissection of important signaling networks and development of drugs with fewer side effects.
DE-ORPHANs design hypotheses are based on unique computational methods to analyze protein and ligand similarities and are founded on genomic and protein sequences, structural data and ligands. The interdisciplinary research strategy applies multiple ligands acting independently but in concert to provide complementary receptor characterization. The results will allow the research field to advance into studies of receptor functions and exploitation of druggable targets, ligands and mechanisms. Which physiological insights and therapeutic breakthroughs will we witness when these receptors find their place in human pharmacology and medicine?

SummaryCellular processes are largely governed by sophisticated protein posttranslational modification (PTM)-dependent signaling networks, and a systematic understanding of regulatory PTM-based networks is a key goal in modern biology. Ubiquitin is a small, evolutionarily conserved signaling protein that acts as a PTM after being covalently conjugated to other proteins. Reversible ubiquitylation forms the most versatile and largest eukaryote-exclusive signaling system, and regulates the stability and function of almost all proteins in cells. Deubiquitylases (DUBs) are ubiquitin-specific proteases that remove substrate-conjugated ubiquitin, and thereby regulate virtually all ubiquitylation-dependent signaling. Because of their central role in ubiquitin signaling, DUBs have essential functions in mammalian physiology and development, and the dysregulated expression and mutation of DUBs is frequently associated with human diseases. Despite their vital functions, very little is known about the proteins and ubiquitylation sites that are regulated by DUBs and this knowledge gap is hampering our understanding of the molecular mechanisms by which DUBs control diverse biological processes. Recently, we developed a mass spectrometry-based proteomics approach that allowed unbiased and site-specific quantification of ubiquitylation on a systems-wide scale. Here we propose to comprehensively investigate DUB-regulated ubiquitin signaling in human cells. We will integrate interdisciplinary approaches to develop next-generation cell models and innovative proteomic technologies to systematically decode DUB function in human cells. This will enable a novel and detailed understanding of DUB-regulated signaling networks, and open up new avenues for further research into the mechanisms and biological functions of ubiquitylation and of ubiquitin-like modifiers.

Cellular processes are largely governed by sophisticated protein posttranslational modification (PTM)-dependent signaling networks, and a systematic understanding of regulatory PTM-based networks is a key goal in modern biology. Ubiquitin is a small, evolutionarily conserved signaling protein that acts as a PTM after being covalently conjugated to other proteins. Reversible ubiquitylation forms the most versatile and largest eukaryote-exclusive signaling system, and regulates the stability and function of almost all proteins in cells. Deubiquitylases (DUBs) are ubiquitin-specific proteases that remove substrate-conjugated ubiquitin, and thereby regulate virtually all ubiquitylation-dependent signaling. Because of their central role in ubiquitin signaling, DUBs have essential functions in mammalian physiology and development, and the dysregulated expression and mutation of DUBs is frequently associated with human diseases. Despite their vital functions, very little is known about the proteins and ubiquitylation sites that are regulated by DUBs and this knowledge gap is hampering our understanding of the molecular mechanisms by which DUBs control diverse biological processes. Recently, we developed a mass spectrometry-based proteomics approach that allowed unbiased and site-specific quantification of ubiquitylation on a systems-wide scale. Here we propose to comprehensively investigate DUB-regulated ubiquitin signaling in human cells. We will integrate interdisciplinary approaches to develop next-generation cell models and innovative proteomic technologies to systematically decode DUB function in human cells. This will enable a novel and detailed understanding of DUB-regulated signaling networks, and open up new avenues for further research into the mechanisms and biological functions of ubiquitylation and of ubiquitin-like modifiers.

Max ERC Funding

1 972 570 €

Duration

Start date: 2015-10-01, End date: 2020-09-30

Project acronymGRANN

ProjectGraphene Coated Nanoparticles and Nanograins

Researcher (PI)Liv Haahr Hornekaer

Host Institution (HI)AARHUS UNIVERSITET

Call DetailsConsolidator Grant (CoG), PE4, ERC-2014-CoG

SummaryIn a truly cross-disciplinary research project encompassing surface science, optics, nano-science, astrophysics and chemistry we will synthesize a novel family of high quality mono-layer graphene coated nanoparticles and graphene nanograins with new chemical and optical properties and investigate their catalytic activity, chemical stability and optical characteristics to gauge their relevance for and applicability in industrial catalysis, solar cells, and interstellar chemistry.
This will be accomplished by extending existing expertise, knowledge and methods developed by us and by international colleagues for graphene synthesis, graphene reactivity and chemical functionalization, graphene coatings on industrially relevant samples and interstellar surface astrochemistry on carbonaceous materials, into the nanoparticle regime. Combined with state-of-the-art surface science characterization methods with emphasis on scanning tunnelling microscopy and spectroscopy, high resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and thermal desorption mass spectrometry, complemented by Raman and transmission spectroscopy, this will enable us to design, characterize, and understand the properties of this new family of particles at the atomic level.
The vision is to harness and combine the remarkable properties of graphene and nanoparticles to create systems with entirely new and unexplored characteristics, to tune these characteristics to be useful for real-world applications, and to exploit the new systems as the first realistic laboratory models of catalytic nanoparticles for interstellar surface chemistry.
This ambitious and cross-disciplinary research program will predominantly take place at the Surface Dynamics Laboratory at Aarhus University which is headed by the applicant, but will also involve local, national and international collaborators.

In a truly cross-disciplinary research project encompassing surface science, optics, nano-science, astrophysics and chemistry we will synthesize a novel family of high quality mono-layer graphene coated nanoparticles and graphene nanograins with new chemical and optical properties and investigate their catalytic activity, chemical stability and optical characteristics to gauge their relevance for and applicability in industrial catalysis, solar cells, and interstellar chemistry.
This will be accomplished by extending existing expertise, knowledge and methods developed by us and by international colleagues for graphene synthesis, graphene reactivity and chemical functionalization, graphene coatings on industrially relevant samples and interstellar surface astrochemistry on carbonaceous materials, into the nanoparticle regime. Combined with state-of-the-art surface science characterization methods with emphasis on scanning tunnelling microscopy and spectroscopy, high resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and thermal desorption mass spectrometry, complemented by Raman and transmission spectroscopy, this will enable us to design, characterize, and understand the properties of this new family of particles at the atomic level.
The vision is to harness and combine the remarkable properties of graphene and nanoparticles to create systems with entirely new and unexplored characteristics, to tune these characteristics to be useful for real-world applications, and to exploit the new systems as the first realistic laboratory models of catalytic nanoparticles for interstellar surface chemistry.
This ambitious and cross-disciplinary research program will predominantly take place at the Surface Dynamics Laboratory at Aarhus University which is headed by the applicant, but will also involve local, national and international collaborators.

Max ERC Funding

1 996 147 €

Duration

Start date: 2015-07-01, End date: 2020-06-30

Project acronymHADES

ProjectBenthic diagenesis and microbiology of hadal trenches

Researcher (PI)Ronnie N Glud

Host Institution (HI)SYDDANSK UNIVERSITET

Call DetailsAdvanced Grant (AdG), PE10, ERC-2014-ADG

SummaryWith this project, called HADES, we aim to provide the first detailed, combined analysis of benthic diagenesis and microbial ecology of some of the deepest oceanic trenches on Earth. We argue that deep trenches, some of the most remote, extreme, and scantly explored habitats on Earth, are hotspots of deposition and mineralization of organic material. With the development of novel autonomous in situ instrumentation to overcome large sampling artifacts from decompression, we will i) determine rates of benthic metabolism and the importance of the deep trenches for the marine carbon and nitrogen cycles, ii) explore the unique benthic microbial communities driving these processes, and iii) investigate the proposed great role of virus in regulating microbial performance and carbon cycling in hadal sediments. By comparing trenches from contrasting oceanic settings the project provides a completely novel general analysis of hadal biogeochemistry and the role of deep trenches in the oceans, as well as fundamental new insights into the composition and functioning of microbial communities at extreme pressure.

With this project, called HADES, we aim to provide the first detailed, combined analysis of benthic diagenesis and microbial ecology of some of the deepest oceanic trenches on Earth. We argue that deep trenches, some of the most remote, extreme, and scantly explored habitats on Earth, are hotspots of deposition and mineralization of organic material. With the development of novel autonomous in situ instrumentation to overcome large sampling artifacts from decompression, we will i) determine rates of benthic metabolism and the importance of the deep trenches for the marine carbon and nitrogen cycles, ii) explore the unique benthic microbial communities driving these processes, and iii) investigate the proposed great role of virus in regulating microbial performance and carbon cycling in hadal sediments. By comparing trenches from contrasting oceanic settings the project provides a completely novel general analysis of hadal biogeochemistry and the role of deep trenches in the oceans, as well as fundamental new insights into the composition and functioning of microbial communities at extreme pressure.

SummaryCyber-physical systems (CPS) are emerging throughout society, e.g. traffic systems, smart grids, smart cities, and medical devices, and brings the promise to society of better solutions in terms of performance, efficiency and usability. However, CPS are often highly safety critical, e.g. cars or medical devices, thus the utmost care must be taken that optimization of performance does not hamper crucial safety conditions. Given the constant growth in complexity of CPS, this task is becoming increasingly demanding for companies to handle with existing methods. The principle barrier for mastering the engineering of complex CPS being both trustworthy and efficient is the lack of a theoretical well-founded framework for CPS engineering supported by powerful tools, that will enable companies to timely meet increasing market demands.
With his extensive contributions to model-driven methodologies, and as provider of one of the “foremost” tools for embedded systems verification, the PI is well prepared to provide the missing framework. The LASSO framework will support the quantitative modeling of both cyber- and physical components, their efficient analysis, the learning of models for unknown components, as well as automatic synthesis and optimization of missing cyber-components from specifications. LASSO will provide the new generation of scalable tools for CPS, allowing trade-offs between safety constraints and performance measure to be made.
LASSO will achieve its objective by ground-breaking and extensive combinations of two different research areas: model checking and machine learning. The framework will develop a complete metric approximation theory for quantitative models, allowing properties to be inferred from reduced or learned models with metric guarantees of their validity in the original system. Further, the applicability of the framework will be validated through a number of CPS case studies, and the tools developed will be made generally available.

Cyber-physical systems (CPS) are emerging throughout society, e.g. traffic systems, smart grids, smart cities, and medical devices, and brings the promise to society of better solutions in terms of performance, efficiency and usability. However, CPS are often highly safety critical, e.g. cars or medical devices, thus the utmost care must be taken that optimization of performance does not hamper crucial safety conditions. Given the constant growth in complexity of CPS, this task is becoming increasingly demanding for companies to handle with existing methods. The principle barrier for mastering the engineering of complex CPS being both trustworthy and efficient is the lack of a theoretical well-founded framework for CPS engineering supported by powerful tools, that will enable companies to timely meet increasing market demands.
With his extensive contributions to model-driven methodologies, and as provider of one of the “foremost” tools for embedded systems verification, the PI is well prepared to provide the missing framework. The LASSO framework will support the quantitative modeling of both cyber- and physical components, their efficient analysis, the learning of models for unknown components, as well as automatic synthesis and optimization of missing cyber-components from specifications. LASSO will provide the new generation of scalable tools for CPS, allowing trade-offs between safety constraints and performance measure to be made.
LASSO will achieve its objective by ground-breaking and extensive combinations of two different research areas: model checking and machine learning. The framework will develop a complete metric approximation theory for quantitative models, allowing properties to be inferred from reduced or learned models with metric guarantees of their validity in the original system. Further, the applicability of the framework will be validated through a number of CPS case studies, and the tools developed will be made generally available.